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Signaling Landscape of AML: The Story So Far

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Book cover Recent Trends in Cancer Biology: Spotlight on Signaling Cascades and microRNAs

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Abstract

Acute myeloid leukemia (AML) is the most frequent leukemia in adults and presents a very high incidence all over the world. The most important aberrations involve mutations and large chromosomal translocations in the genes responsible for hematopoiesis, resulting in an abnormal signal transduction activation that boosts survival and proliferation of progenitor cells and a typical accumulation of poorly differentiated myeloid cells. Acute myeloid leukemia is an extremely complex malignancy with considerable genetic, epigenetic, and phenotypic heterogeneity. Most AML genomes present very few mutations, which are responsible for the aberrant phenotypes observed. The possibility to characterize the mutations present in single cells and the studies on hematopoiesis performed both in vitro and in vivo, make AML an ideal model for investigating the underlying mechanisms of tumorigenesis. In the last years, the signaling proteins identified as specifically mutated in AML have raised huge consideration as attractive therapeutic targets and many efforts are currently ongoing in order to design ad hoc strategies to improve prognosis and therapy. Recent advances in the conventional treatments, together with innovative therapies, show significant promises for curing AML patients.

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Abbreviations

ALCL:

Anaplastic large cell lymphomas

AML:

Acute myeloid leukemia

APL:

Acute promyelocitic leukemia

ATRA:

All-trans retinoic acid

CART:

Chimeric antigen receptor T-cell

CBF:

Core binding factor

CK:

Complex karyotype

CN:

Cytogenetically normal

CR:

Complete remission

DNMT:

DNA methyltransferases

FAB:

French American British

GO:

Gemtuzumab ozogamicin

HDAC:

Histone deacetylase

HMA:

Hypomethylating agent

ITD:

Internal tandem duplication

MEF:

Mouse embryonic fibroblast

NCCN:

National comprehensive cancer network clinical guidelines in oncology

OS:

Overall survival

PTD:

Partial tandem duplication

RTK:

Receptor tyrosine kinase

scFv:

Single chain variable fragment

TKD:

Tyrosine kinase domain

WHO:

World health organization

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Authors and Affiliations

  1. Department of Biosciences, University of Milan, Milan, Italy

    Chiara Martinelli

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  1. Chiara Martinelli
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Correspondence to Chiara Martinelli .

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  1. Department of Biochemistry, Rashid Latif Medical College (RLMC), Lahore, Pakistan

    Sundas Fayyaz

  2. Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

    Ammad Ahmad Farooqi

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Martinelli, C. (2018). Signaling Landscape of AML: The Story So Far. In: Fayyaz, S., Farooqi, A. (eds) Recent Trends in Cancer Biology: Spotlight on Signaling Cascades and microRNAs. Springer, Cham. https://doi.org/10.1007/978-3-319-71553-7_13

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